This project will link an existing population level dataset consisting of all California births between 1996 and 2006 (over five million children, over 60,000 twin pairs, and over 1 million full and half sibling groups) and outcome data on autism and receipt of developmental services to the CDC's National Assisted Reproductive Technology Surveillance System registry for California infertility clinics for the same period. We will use ths detailed dataset from a large ethnically and geographically diverse state to assess the relationship, if any, between Assisted Reproductive Technology (ART), including in vitro fertilization and related procedures, and autism and to identify the pathways through which this association operates. ART and autism have both increased rapidly in recent decades, and although a relationship is widely suspected, existing research has reported mixed and inconclusive findings, largely a result of insufficient samples. Our design, which enables us to identify about 50,000 ART births and about 24,000 cases of autistic disorder over ten consecutive years, overcomes previous limitations and promises to enable an accurate estimation of autism risk associated with ART. Further, the detailed information we will have on child, parent and family characteristics, residence at birth, ART methods and procedures, and autism outcomes will allow us to better understand the mechanisms at play. With this information, we can 1) identify whether such an association is confounded by individual characteristics selective for both autism and ART, such as parental age, SES, and infertility factors; 2) identify whether an observed association between ART and autism is uniform across ART protocols or is specific to certain method(s); 3) explore the role of clinic-level factors; and 4) ascertain the temporal and spatial correlates of the association of ART and autism. Against the background of rapidly rising autism prevalence and the increasingly important role of ART in reproductive decision-making, this research has important scientific and public health implications. This project has the potential to make significant contributions to our understanding of the etiology of autism as well as the long-term outcomes of ART births, neither of which are well understood. PUBLIC HEALTH RELEVANCE: The prevalence of autism has increased rapidly over the last three decades, although its causes remain poorly understood; meanwhile the use of Assisted Reproductive Technology (ART) has also increased dramatically, although the long-term risks to children conceived this way remain largely unknown. This project will contribute to public health by creating a unique population- level dataset designed to ascertain any potential association between ART or its subtypes and autism as well as identify the mechanisms of the association. This will better enable individuals and their health care providers to weigh the risks and benefits of ART procedures and to recognize a potentially modifiable risk factor for autism.